PloS one, 2014-03, Vol.9 (3), p.e91983
2014
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- Autor(en) / Beteiligte
- Titel
- The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer
- Ist Teil von
- PloS one, 2014-03, Vol.9 (3), p.e91983
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Pancreatic cancer stem cells (CSCs) represent a small subpopulation of pancreatic cancer cells that have the capacity to initiate and propagate tumor formation. However, the mechanisms by which pancreatic CSCs are maintained are not well understood or characterized. Expression of Notch receptors, ligands, and Notch signaling target genes was quantitated in the CSC and non-CSC populations from 8 primary human pancreatic xenografts. A gamma secretase inhibitor (GSI) that inhibits the Notch pathway and a shRNA targeting the Notch target gene Hes1 were used to assess the role of the Notch pathway in CSC population maintenance and pancreatic tumor growth. Notch pathway components were found to be upregulated in pancreatic CSCs. Inhibition of the Notch pathway using either a gamma secretase inhibitor or Hes1 shRNA in pancreatic cancer cells reduced the percentage of CSCs and tumorsphere formation. Conversely, activation of the Notch pathway with an exogenous Notch peptide ligand increased the percentage of CSCs as well as tumorsphere formation. In vivo treatment of orthotopic pancreatic tumors in NOD/SCID mice with GSI blocked tumor growth and reduced the CSC population. The Notch signaling pathway is important in maintaining the pancreatic CSC population and is a potential therapeutic target in pancreatic cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0091983Titel-ID: cdi_plos_journals_1508765015
- Format
- –
- Schlagworte
- Animals, Apoptosis, Basic Helix-Loop-Helix Transcription Factors - genetics, Basic Helix-Loop-Helix Transcription Factors - metabolism, Biology and Life Sciences, Brain cancer, Brain research, Breast cancer, Cancer, Cancer therapies, Cell growth, Chemotherapy, Consent, Departments, Disease Models, Animal, Gene expression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic - drug effects, Homeodomain Proteins - genetics, Homeodomain Proteins - metabolism, Humans, Inhibitors, Ligands, Medical research, Medicine and Health Sciences, Metastasis, Mice, Inbred NOD, Mice, SCID, Neoplastic Stem Cells - drug effects, Neoplastic Stem Cells - metabolism, Neoplastic Stem Cells - pathology, Notch protein, Pancreatic cancer, Pancreatic Neoplasms, Pancreatic Neoplasms - genetics, Pancreatic Neoplasms - metabolism, Pancreatic Neoplasms - pathology, Protease Inhibitors - pharmacology, Receptors, Receptors, Notch - metabolism, Research and Analysis Methods, Review boards, RNA, Small Interfering - metabolism, Secretase, Signal transduction, Signal Transduction - drug effects, Signaling, Spheroids, Cellular - drug effects, Spheroids, Cellular - metabolism, Spheroids, Cellular - pathology, Stem cell transplantation, Stem cells, Surgery, Transcription Factor HES-1, Tumor Cells, Cultured, Tumorigenesis, Tumors, Up-Regulation - drug effects, Xenografts